Guanylate-binding proteins (GBPs) belong to the family of large GTPases that are induced in response to interferons. GBPs contain an N-terminal globular GTPase domain and a C-terminal α-helical regulatory domain that are connected by a short middle domain.
Antiviral activity against vesicular stomatitis virus and encephalomyocarditis virus has been shown for hGBP-1; however, no anti-influenza virus properties for GBPs have been described to date.
Here we show that hGBP-1 and hGBP-3 possess anti-influenza viral activity. Furthermore, we have identified a novel splice variant of hGBP-3, named hGBP-3ΔC, with a largely modified C-terminal α-helical domain.
While all three GBP isoforms were up-regulated on influenza virus infection, hGBP-3ΔC showed the most prominent antiviral activity in epithelial cells.
Mutational analysis of hGBPs revealed that the globular domain is the principal antiviral effector domain, and GTP-binding, but not hydrolysis, is necessary for antiviral action. Furthermore, we showed that hGBP-3ΔC strongly represses the activity of the viral polymerase complex, which results in decreased synthesis of viral vRNA, cRNA, mRNA, and viral proteins, as well.
2012-03-01
Eng.
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Institute of Molecular Virology (IMV), Centre for Molecular Biology of Inflammation (ZMBE), Westfaelische Wilhelms-University, Von-Esmarch-Str. 56, D-48149 Muenster, Germany.
FASEB J. 2012 Mar;26(3):1290-300
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